Pathophysiology and Evaluation of Dyslipidemia Flashcards
What is the significance of dyslipidemia?
-Lipoprotein abnormalities can contribute to increased risk for coronary, cerebrovascular, and peripheral arterial disease
-Coronary atherosclerosis contributes to ischemic heart disease
Examples of lipids
-Cholesterol
-Cholesterol esters
-Triglycerides
-Phospholipids
Examples of lipoproteins
-LDL
-HDL
-VLDL
Examples of apolipoproteins
-Apo-B
-Apo-A1
-Apo-CIII
Symptoms of dyslipidemia
-Largely asymptomatic
-Chest pain
-Palpitations
-Sweating
-Anxiety
-Shortness of breath
-Loss of consciousness
-Abdominal pain
-Sudden death
Warning signs of dyslipidemia
-Pancreatitis
-Eruptive xanthomas
-Peripheral polyneuropathy
-Increased BP
-Waist size (>40 inches in men) (>35 inches in women)
-BMI over 30
Significant lab parameters associated with dyslipidemia
-Increased non-HDL-C
-Increased TC
-Increased LDL-C
-Increased TG
-Increased Apo-B
-Increased CRP
-Increased LDL-P
-Decreased HDL
What is included in a fasting lipid panel?
-TC
-TG
-HDL-C
-LDL-C
-Calculated using the Friedewald equation
What is the Friedewald equation?
LDL = TC - HDL - TG/5
When is the Friedewald equation not valid?
When TG is over 400
How do you calculate non-HDL-C using the Friedewald equation?
non-HDL-C = LDL-C + TG/5
What are the non-pharmacologic ways to treat dyslipidemia?
-DASH dietary pattern, USDA food pattern, or AHA diet
-Reduce percent of calories from saturated and trans fat
-Lower sodium intake
-Engage in moderate-to-vigorous intensity aerobic physical exercise
-Smoking cessation
What are some examples of foods that would be an appropriate diet to treat dyslipidemia?
-Vegetables, fruits and whole grains
-Low-fat dairy products, poultry, fish, legumes
-Non-tropical vegetable oils and nuts
-Limit sweets and red meats
What percent of saturated fats is acceptable when treating dyslipidemia?
5-6% calories from saturated fats
How much should you lower daily sodium intake by when treating dyslipidemia?
-Less than 1500 mg/day
-Aim for a reduction of at least 1000 mg/day for most adults
How much exercise would people with dyslipidemia do weekly?
90-150 min per week
What were the results of the REDUCE-IT trial?
3.1% of patients taking icosapent ethyl were hospitalized for AF or atrial flutter compared to 2.1% of the placebo group
What were the results of the OMEMI trial?
7.2% of patients taking n-3 PUFA (EPA and DHA) had AF compared to 4% of placebo patients
What were the results of the STRENGTH trial?
Omega-3 carboxylic acid-treated group 2.2% had AF compared to 1.3% in the corn oil group
What are the HMG-CoA reductase inhibitors?
-Lovastatin
-Pravastatin
-Pitavastatin
-Simvastatin
-Fluvastatin
-Atorvastatin
-Rosuvastatin
What are the low intensity statins?
-Simvastatin 10 mg
-Pravastatin 10-20 mg
-Lovastatin 20 mg
-Fluvastatin 20-40 mg
What are the moderate intensity statins?
-Atorvastatin 10-20 mg
-Rosuvastatin 5-10 mg
-Simvastatin 20-40 mg
-Pravastatin 40-80 mg
-Lovastatin 40-80 mg
-Fluvastatin 40 mg BID
-Fluvastatin XL 80 mg
-Pitavastatin 1-4 mg
What are the high intensity statins?
-Atorvastatin 40-80 mg
-Rosuvastatin 20-40 mg
Which statins are hydrophilic?
-Pravastatin
-Rosuvastatin
Which statins are degraded by CYP 3A4?
-Lovastatin
-Simvastatin
-Atorvastatin
Important considerations for statins
-Usually well-tolerated
-Obtain LFTs at baseline (DC if LFTs 3x upper limit of normal)
-Serious muscle toxicity (myopathy and rhabdomyolysis)
-Watch for unusual muscle pain and darkened urine
-Avoid large quantities of grapefruit juice (>1 quart daily)
-Contraindicated in pregnant women or women who may become pregnant
Characteristics that predispose individuals to statin adverse effects
-Impaired renal or hepatic function
-Prior statin intolerance or muscle disorders
-Unexplained ALT elevations of 3x ULN
-Other drugs that affect statin metabolism
-Over 75 years of age
What to do when patient experiences muscle symptoms or fatigue while on statin
-DC statin and evaluate for rhabdomyolysis
-Evaluate for exacerbating conditions
-Restart same or lower dose statin once symptoms resolve
Statin contraindications
-Acute liver disease
-Unexplained, persistent elevations of serum transaminases
-Pregnancy
-Breastfeeding
How do you manage statin treatment for a patient experiencing symptoms of muscle injury?
-Ensure the patient has a valid indication for statins
-Assess if muscle pain is exercise-related
-DC the statin and see if muscle pain resolves
-Switch to a lower risk statin (hydrophilic statins)
-Consider alternative dosing strategies
-Consider DC the statin/using alternative agents
Alternative dosing strategies for statins
-Every other day and once weekly statin dosing has been suggested to improve utilization or tolerability and decrease cost
-Initial data for atorvastatin, fluvastatin, and rosuvastatin suggest that double the daily dose is necessary for every other day dosing to achieve similar LDL lowering
Contraindications with simvistatin
-Itraconazole
-Ketoconazole
-Posaconazole
-Erythromycin
-Clarithromycin
-Telithromycin
-HIV protease inhibitors
-Nefazodone
-Gemfibrozil
-Cyclosporine
-Danazol
Which drugs should you not exceed 10 mg simvastatin daily with?
-Verapamil
-Diltiazem
Which drugs should you not exceed 20 mg simvastatin daily with?
-Amiodarone
-Amlodipine
-Ranolazine
When should FLP be monitored when on a statin?
-At baseline
-4-12 weeks following statin initiation
-Every 2-12 months, as clinically indicated
What are the bile acid resins?
-Cholestyramine
-Colestipol
-Colesevelam
Disadvantages associated with BARs
-May increase TG
-Must take other medications one hour before or 4 hours after BAR
Adverse effects associated with BARs
-Constipation
-Bloating
-Nausea
-Flatulence
-Impaired absorption of fat-soluble vitamins
-Hypernatremia
-Hyperchloremia
-GI obstruction
What is cholestyramine contraindicated in?
Complete biliary obstruction
What is colesevelam contraindicated in?
-History of bowel obstruction
-Serum TG over 500
-History of hypertriglyceridemia-induced pancreatitis
What can BARs interact with?
May decrease the effects of:
-Acetaminophen
-TZDs
-Oral contraceptives
-Corticosteroids
-Ezetimibe
-Fibrates
-Thiazide diuretics
-Warfarin
-Digoxin
Niacin contraindications
-Active hepatic disease
-Significant or unexplained persistent liver transaminase elevations
-Active peptic ulcer
-Arterial hemorrhage
What is the cholesterol absorption inhibitor?
Ezetimibe
What is the combination product that contains ezetimibe and simvistatin?
Vytorin
How much can ezetimibe decrease LDL by when paired with a statin?
12-20%
Adverse effects associated with ezetimibe
-Fatigue
-Diarrhea
-GI upset
Ezetimibe contraindications
-Concomitant use with a statin and active hepatic disease or unexplained persistent serum transaminase elevations
-Pregnancy (when used with a statin)
-Breast feeding (when used with a statin)
Fibrate side effects
-GI disturbances
-Rash
-Myalgia
-Dizziness
Fibrate contraindications
-History of gallbladder disease
-ESRD or dialysis
-Persistent liver disease
What can fibrates increase the levels of?
-Statins
-Ezetimibe
-Sulfonylureas
-Warfarin
What are the PCSK9 monoclonal antibodies?
-Alirocumab
-Evolocumab
What are PCSK9 inhibitors indicated in?
Adjunct to diet and statin to reduce LDL in familial heterozygous hypercholesterolemia or atherosclerotic CVD
PCSK9 adverse effects
-GI upset
-Increased LFTs
-Injection site reaction
-Myalgia
-Influenza
Inclisiran indication
Adjunct to diet and statin to reduce LDL in familial heterozygous hypercholesterolemia or atherosclerotic CVD
Inclisiran adverse effects
-Injection site reactions
-Arthralgia
-Urinary tract infection
-Diarrhea
-Bronchitis
-Pain in extremities
-Dyspnea
Bempedoic acid indication
Adjunct to diet and statin to reduce LDL in familial heterozygous hypercholesterolemia or atherosclerotic CVD
Adverse reactions to bempedoic acid
-URTI
-Muscle spasms
-Hyperuricemia
-Back pain
-Abdominal pain
-Bronchitis
-Pain in extremity
-Anemia
-Elevated liver enzymes
Warnings and precautions to bempedoic acid
-May increase blood uric acid levels and lead to the development of gout
-Risk of tendon rupture
-Avoid concomitant use with simvastatin >20 mg and pravastatin >40 mg (myopathy)
What is in red yeast rice that allows it to be used as an additional medication?
Lovastatin
How is persistent hypertriglyceridemia defined?
Fasting TG over 150 following at least 4-12 weeks of lifestyle intervention, a stable dose of a maximally tolerated statin, and a secondary cause evaluation
What is defined as moderate hypertriglyceridemia?
150-499
What is defined as severe hypertriglyceridemia?
over 500
Lifestyle modifications to reduce TG
-Targeting 5-10% weight loss = 20% decrease in TG
-Very low fat diet (10-15% of diet); restriction of alcohol, sugar, and reined carbs
-Moderate or high intensity physical exercise (150 or more min per week)
Pharmacologic treatment of TG
Fibrates or omega-3 fatty acids are the go-to
